Since the invention of penicillin in 1928 by Alexander Flemming and their wider availability in the 1940s, further variants of existing and new antibiotics have been on the trial. Compared to the situation in 1954 when two million pounds of antibiotics were produced in the US, the present figure exceeds 50 million pounds. Antibiotics work either by killing bacteria (bacteriocidal) or by inhibiting growth (bacteriostatic) and their bioactivities have transformed human ability to treat many infectious diseases that previously were considered certain killers. It is estimated that globally humans consume above 250 million doses of antibiotics annually and 20%–50% of that use is unnecessary depending on the class of antibiotic. Further, widespread use of antibiotics promotes spread of antibiotic resistance many a times leading to multiple drug resistance. The total amount of antibiotic in the given dosage used for treatment of an infection generally is much higher than what is actually required to control a given population of parasite in the infected individual. This is so because all antibiotic given to the patient in a therapy does not reach the target site. This may be due to (i) lower absorption in the gut membrane when taken orally (ii) restrictive uptake by the target microbe or (iii) operation of efflux pump leading to indiscriminate extrusion of the antibiotics or therapeutic molecules. Thus, large portions of the drugs we apply are wasted and only a miniscule percentage is being targeted to the infective microbes. But even worse part is that the unutilized drug/antibiotic amount remains as a load in the body and environment. This then acts as a selection pressure, facilitating emergence of drug resistance in parasites leading to their predominance in the niche and ultimately resulting into failure of antibiotics against resistant infections. Additionally, such a situation leads to side effects, illness and reduction in life expectancy being more acute in the older population. One of the ways that has been feasible to reduce drug dosage is the occurrence of synergism between different therapeutic agents. However, even in such a situation if both the molecules have the antibiotic property, the problem of continued selection pressure on microbes is still likely to continue. Therefore, the need is for molecules, which by themselves are not microbicidal but when present with a drug or active molecule, enhance its activity and availability (bioenhancers). These molecules by their presence will not exert any selection pressure for the mutants to emerge resistant against them and on the other hand could reduce the dosage of antibiotics or drugs so that their ill effects are minimized. This way resistance development process will be substantially delayed ultimately leading to enhanced life-span of the novel and existing antibiotics. Such drug/molecule facilitators should have novel properties like non-toxic to humans, animals or plants, should be effective at a very low concentration in a combination, should be easy to formulate and most importantly enhance uptake/absorption and activity of the drug molecules. This can lead to development of judicious and strategic concentrations of antibiotics with specific bioenhancers to improve availability of the drug right up to the target for effectively controlling the infectious organisms.
The present invention was the result of planned experiments to provide a novel method for improving activity and bioavailability of antibiotics, drugs and other molecules using a plant glycoside “Glycyrrhizin” in different formulations.
The bioavailability of nutrients and enhancement of antibiotics/drugs effectivity is relevant to human, plant as well as animal health and thus the compositions and methods of the invention are also intended to be used in agriculture and veterinary practice.